US 5,288,722 AGranted

6-amino-6-desoxyfumagillols, production and use thereof

AssigneeTakeda Chemical Industries, Ltd.

InventorsShoji Kishimoto, Shogo Marui, Takeshi Fujita

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Abstract

The present invention relates to a compound of the formula: ##STR1## wherein R.sup.1 is 2-methyl-1-propenyl group or isobutyl group; R.sup.2 and R.sup.3 are each hydrogen atom, an optionally substituted hydrocarbon residue or an optionally substituted acyl group or R.sup.2 and R.sup.3 may form a ring together with the adjacent nitrogen atom; and the bonding mark .about. represents an .alpha.-linkage or .beta.-linkage, or a salt thereof. The compound (I) of the present invention has, among others, angiogenesis inhibiting activity, cell-growth inhibiting activity and immune reaction inhibiting activity, thus being useful as medicines, etc.

Claims8

Dependent claims

A compound of the formula:

##STR8## wherein R.sup.1 is 2-methyl-1-propenyl group or isobutyl group;
R.sup.2 is
(1) hydrogen atom,
(2) a C.sub.1-20 alkyl group which may be substituted with (i) amino, (ii) C.sub.1-6 alkylamino, (iii) di-C.sub.1-6 alkylamino, (iv) nitro, (v) halogen, (vi) hydroxyl, (vii) C.sub.1-6 alkylthio, (viii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 carbamoyl, (ix) carboxyl, (xii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 alkoxy, (xiv) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, or
(3) a C.sub.6-12 aryl group which may be substituted with (i) C.sub.2-6 alkyl, (ii) amino, (iii) halogen, (iv) hydroxyl, (v) C.sub.1-6 alkoxy, (vi) cyano, (vii) carbamoyl or (viii) carboxyl;
R.sup.3 is
(1) hydrogen atom,
(2) a C.sub.1-20 alkyl group which may be substituted with (i) amino, (ii) C.sub.1-6 alkylamino, (iii) di-C.sub.1-6 alkylamino, (iv) nitro, (v) halogen, (vi) hydroxyl, (vii) C.sub.1-6 alkylthio, (viii) C.sub.1-6 alkoxy, (ix) cyano, (x) carbamoyl, (xi) carboxyl, (xii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 alkoxy, (xiv) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, or (xv) a 5- to 6-membered aromatic heterocyclic group containing 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and the said alkyl group may be epoxidated at an optional position,
(3) a C.sub.2-20 alkanoyl group which may be substituted with (i) amino, (ii) C.sub.1-6 alkylamino, (iii) di-C.sub.1-6 alkylamino, (iv) nitro, (v) halogen, (vi) hydroxyl, (vii) C.sub.1-6 alkylthio, (viii) C.sub.1-6 alkoxy, (ix) cyano, (x) carbamoyl, (xi) carboxyl, (xii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 alkoxy, (xiv) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, or (xv) a 5- to 6-membered aromatic heterocyclic group containing 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur,
(4) a C.sub.6-10 aroyl group which may be substituted with (i) C.sub.2-6 alkyl, (ii) amino, (iii) halogen, (iv) hydroxyl, (v) C.sub.1-6 alkoxy, (vi) cyano, (vii) carbamoyl or (viii) carboxyl,
(5) carbamoyl group which may be substituted with Ii) C.sub.1-6 alkyl, (ii) C.sub.1-6 alkanoyl, (iii) halogeno-C.sub.1-6 alkanoyl, (iv) C.sub.1-6 alkoxycarbonylmethyl, (v) carboxymethyl, (vi) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, (vii) naphthyl, (viii) benzoyl, (ix) naphthoyl or (x) substituents forming cyclic amino group, taken together with the nitrogen atom of the carbamoyl group,
(6) benzenesulfonyl group which may be substituted with (i) C.sub.1-6 alkyl or (ii) halogen,
(7) a C.sub.1-6 alkylsulfonyl group which may be substituted with the same substituents(s) as those of substituted C.sub.2-20 alkanoyl group mentioned in above (3),
(8) thiocarbamoyl group which may be substituted with the same substituents(s) as those of a substituted carbamoyl group mentioned in above (5),
(9) a C.sub.1-6 alkoxycarbonyl group which may be substituted with the same substituent(s) as those of a substituted C.sub.2-20 alkanoyl group mentioned in above (3),
(10) phenoxycarbonyl group which may be substituted with the same substituent(s) as those of a substituted benzenesulfonyl group mentioned in above (6), or
(11) a 5- or 6-membered aromatic heterocyclic carbonyl group containing 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur which may be substituted with the same substituent(s) as those of a substituted C.sub.6-10 aroyl group mentioned in above (4), wherein said aromatic heterocyclic carbonyl group is selected from the group consisting of 2-furoyl, 2-thenoyl, nicotinoyl and isonicotinoyl;
R.sup.2 and R.sup.3 may form pyrolidine, piperidine or isoindoline ring which may be substituted with C.sub.1-3 alkyl or oxo;
and the bonding mark .about. represents an .alpha.-linkage or .beta.-linkage, or a salt thereof.

16 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of the formula:

##STR8## wherein R.sup.1 is 2-methyl-1-propenyl group or isobutyl group;
R.sup.2 is
(1) hydrogen atom,
(2) a C.sub.1-20 alkyl group which may be substituted with (i) amino, (ii) C.sub.1-6 alkylamino, (iii) di-C.sub.1-6 alkylamino, (iv) nitro, (v) halogen, (vi) hydroxyl, (vii) C.sub.1-6 alkylthio, (viii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 carbamoyl, (ix) carboxyl, (xii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 alkoxy, (xiv) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, or
(3) a C.sub.6-12 aryl group which may be substituted with (i) C.sub.2-6 alkyl, (ii) amino, (iii) halogen, (iv) hydroxyl, (v) C.sub.1-6 alkoxy, (vi) cyano, (vii) carbamoyl or (viii) carboxyl;
R.sup.3 is
(1) hydrogen atom,
(2) a C.sub.1-20 alkyl group which may be substituted with (i) amino, (ii) C.sub.1-6 alkylamino, (iii) di-C.sub.1-6 alkylamino, (iv) nitro, (v) halogen, (vi) hydroxyl, (vii) C.sub.1-6 alkylthio, (viii) C.sub.1-6 alkoxy, (ix) cyano, (x) carbamoyl, (xi) carboxyl, (xii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 alkoxy, (xiv) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, or (xv) a 5- to 6-membered aromatic heterocyclic group containing 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and the said alkyl group may be epoxidated at an optional position,
(3) a C.sub.2-20 alkanoyl group which may be substituted with (i) amino, (ii) C.sub.1-6 alkylamino, (iii) di-C.sub.1-6 alkylamino, (iv) nitro, (v) halogen, (vi) hydroxyl, (vii) C.sub.1-6 alkylthio, (viii) C.sub.1-6 alkoxy, (ix) cyano, (x) carbamoyl, (xi) carboxyl, (xii) C.sub.1-6 alkoxycarbonyl, (xiii) carboxy-C.sub.1-6 alkoxy, (xiv) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, or (xv) a 5- to 6-membered aromatic heterocyclic group containing 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur,
(4) a C.sub.6-10 aroyl group which may be substituted with (i) C.sub.2-6 alkyl, (ii) amino, (iii) halogen, (iv) hydroxyl, (v) C.sub.1-6 alkoxy, (vi) cyano, (vii) carbamoyl or (viii) carboxyl,
(5) carbamoyl group which may be substituted with Ii) C.sub.1-6 alkyl, (ii) C.sub.1-6 alkanoyl, (iii) halogeno-C.sub.1-6 alkanoyl, (iv) C.sub.1-6 alkoxycarbonylmethyl, (v) carboxymethyl, (vi) phenyl which may be substituted by (a) C.sub.1-6 alkyl, (b) C.sub.1-6 alkoxy, (c) halogen, (d) halogenated alkyl or (e) nitro, (vii) naphthyl, (viii) benzoyl, (ix) naphthoyl or (x) substituents forming cyclic amino group, taken together with the nitrogen atom of the carbamoyl group,
(6) benzenesulfonyl group which may be substituted with (i) C.sub.1-6 alkyl or (ii) halogen,
(7) a C.sub.1-6 alkylsulfonyl group which may be substituted with the same substituents(s) as those of substituted C.sub.2-20 alkanoyl group mentioned in above (3),
(8) thiocarbamoyl group which may be substituted with the same substituents(s) as those of a substituted carbamoyl group mentioned in above (5),
(9) a C.sub.1-6 alkoxycarbonyl group which may be substituted with the same substituent(s) as those of a substituted C.sub.2-20 alkanoyl group mentioned in above (3),
(10) phenoxycarbonyl group which may be substituted with the same substituent(s) as those of a substituted benzenesulfonyl group mentioned in above (6), or
(11) a 5- or 6-membered aromatic heterocyclic carbonyl group containing 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur which may be substituted with the same substituent(s) as those of a substituted C.sub.6-10 aroyl group mentioned in above (4), wherein said aromatic heterocyclic carbonyl group is selected from the group consisting of 2-furoyl, 2-thenoyl, nicotinoyl and isonicotinoyl;
R.sup.2 and R.sup.3 may form pyrolidine, piperidine or isoindoline ring which may be substituted with C.sub.1-3 alkyl or oxo;
and the bonding mark .about. represents an .alpha.-linkage or .beta.-linkage, or a salt thereof.

16 more elements